Macitentan

Endothelin (ET)-1 and its receptors (ET A and ET B ) mediate a variety of deleterious effects, such as vasoconstriction, fibrosis, proliferation, hypertrophy, and inflammation. In disease conditions such as PAH, the local ET system is upregulated and is involved in vascular hypertrophy and in organ damage.

• OPSUMIT is an endothelin receptor antagonist (ERA) indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) in adults to reduce the risks of disease progression and hospitalization for PAH ( 1.1 ). 1.1 Pulmonary Arterial Hypertension OPSUMIT is an endothelin receptor antagonist (ERA) indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) in adults to reduce the risks of disease progression and hospitalization for PAH.ICD-10: I27.0

• Pregnancy ( 4.1 ) Hypersensitivity ( 4.2 ) 4.1 Pregnancy OPSUMIT may cause fetal harm when administered to a pregnant woman. OPSUMIT is contraindicated in females who are pregnant.contraindicated

10 mg once daily . Doses higher than 10 mg once daily have not been studied in patients with PAH and are not recommended ( 2.1 ). 2.1 Recommended Dosage The recommended dosage of OPSUMIT is 10 mg once daily for oral administration. Doses higher than 10 mg once daily have not been studied in patients with PAH and are not recommended. 2.2 Pregnancy Testing in Females of Reproductive Potential Exclude pregnancy before initiating treatment with OPSUMIT in females of reproductive potential [see Boxed Warning , Contraindications (4.1) , Warnings and Precautions (5.1) , and Use in Specific Populations (8.3) ] .

ERAs cause hepatotoxicity and liver failure. Obtain baseline liver enzymes and monitor as clinically indicated ( 5.2 ). Fluid retention may require intervention ( 5.3 ). Decreases in hemoglobin ( 5.4 ). Pulmonary edema in patients with pulmonary veno-occlusive disease. If confirmed, discontinue treatment ( 5.5 ). Decreases in sperm count have been observed in patients taking ERAs ( 5.6 ). 5.1 Embryo-fetal Toxicity Based on data from animal reproduction studies, OPSUMIT may cause fetal harm when administered to a pregnant patient and is contraindicated during pregnancy. The available human data for ERAs do not establish the presence or absence of major birth defects related to the use of OPSUMIT. Advise patients who can become pregnant of the potential risk to a fetus. Obtain a pregnancy test prior to initiation of therapy with OPSUMIT. Advise patients who can become pregnant to use effective contraceptive methods prior to initiation of treatment, during treatment, and for one month after discontinuation of treatment with OPSUMIT. When pregnancy is detected, discontinue use as soon as possible [see Dosage and Administration (2.2) , Contraindications (4.1) , and Use in Specific Populations (8.1 , 8.3) ] . 5.2 Hepatotoxicity ERAs have caused elevations of aminotransferases, hepatotoxicity, and liver failure. The incidence of elevated aminotransferases in the study of OPSUMIT in PAH is shown in Table 1.

Clinically significant adverse reactions that appear in other sections of the labeling include: Embryo-fetal Toxicity [see Warnings and Precautions (5.1) ] Hepatotoxicity [see Warnings and Precautions (5.2) ] Fluid Retention [see Warnings and Precautions (5.3) ] Decrease in Hemoglobin [see Warnings and Precautions (5.4) ] Most common adverse reactions (more frequent than placebo by ≥3%) are anemia, nasopharyngitis/pharyngitis, bronchitis, headache, influenza, and urinary tract infection ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Actelion at 1-800-526-7736 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Safety data for OPSUMIT were obtained primarily from one placebo-controlled clinical study in 742 patients with PAH (SERAPHIN study) [see Clinical Studies (14.1) ]. The exposure to OPSUMIT in this trial was up to 3.6 years with a median exposure of about 2 years (N=542 for 1 year; N=429 for 2 years; and N=98 for more than 3 years). The overall incidence of treatment discontinuations because of adverse events was similar across OPSUMIT 10 mg and placebo treatment groups (approximately 11%). Table 2 presents adverse reactions more frequent on OPSUMIT than on placebo by ≥3%.

Lactation: Advise not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary Based on data from animal reproduction studies, OPSUMIT may cause embryo-fetal toxicity, including birth defects and fetal death, when administered to a pregnant female and is contraindicated during pregnancy. There are risks to the mother and the fetus associated with pulmonary arterial hypertension in pregnancy [see Clinical Considerations ] . Available data from postmarketing reports and published literature over decades of use with ERAs in the same class as OPSUMIT have not identified an increased risk of major birth defects; however, these data are limited. Methodological limitations of these postmarketing reports and published literature include lack of a control group; limited information regarding dose, duration, and timing of drug exposure; and missing data. These limitations preclude establishing a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal ERA use. Macitentan was teratogenic in rabbits and rats at all doses tested. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, advise the patient of the risk to a fetus [see Contraindications (4.1) ] . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.

Metabolism

The pharmacokinetics of macitentan and its active metabolite have been studied primarily in healthy subjects. The pharmacokinetics of macitentan are dose proportional over a range from 1 mg to 30 mg after once daily administration.

OPSUMIT has been administered as a single dose of up to and including 600 mg to healthy subjects (60 times the approved dosage). Adverse reactions of headache, nausea and vomiting were observed. In the event of an overdose, standard supportive measures should be taken, as required. Dialysis is unlikely to be effective because macitentan is highly protein-bound.

• Oct 18, 2013NDANDA204410Actelion
• Apr 6, 2021ANDAANDA211224Zydus Lifesciences
• Apr 18, 2023ANDAANDA211198Aurobindo Pharma Ltd
• Jan 9, 2024ANDAANDA211195Apotex
• Mar 22, 2024NDANDA218490Actelion
• Aug 5, 2024ANDAANDA211107Torrent
• Aug 18, 2025ANDAANDA211128Alembic
• Aug 20, 2025ANDAANDA211136Msn

1. 1Dyspnoea11,81917%
2. 2Headache8,18212%
3. 3Death7,33211%
4. 4Diarrhoea6,4909.6%
5. 5Nausea5,8898.7%
6. 6Fatigue4,9637.3%
7. 7Pneumonia4,5116.6%
8. 8Dizziness4,4576.6%
9. 9Hospitalisation4,0796.0%
10. 10Cough3,8645.7%
11. 11Fluid Retention3,8085.6%
12. 12Malaise3,5715.3%
13. 13Hypotension3,5625.2%
14. 14Pulmonary Arterial Hypertension3,2744.8%
15. 15Vomiting3,1554.6%

The 10 most recently updated of 77 ClinicalTrials.gov registrations naming Macitentan as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A Study Providing Treatment Access in Participants With Pulmonary Hypertension Completing a Parent Study and Having no Other Option
  Recruiting · Phase 3 · Interventional · 280 enrolled · Actelion
  NCT05179876updated 2026-06-05
• Outcome Study Assessing a 75 Milligrams (mg) Dose of Macitentan in Patients With Pulmonary Arterial Hypertension
  Active not recruiting · Phase 3 · Interventional · 935 enrolled · Actelion
  NCT04273945updated 2026-06-05
• A Study of Macitentan in Japanese Pediatric Participants With Pulmonary Arterial Hypertension
  Completed · Phase 3 · Interventional · 7 enrolled · Janssen Pharmaceutical K.K.
  NCT05167825updated 2026-05-07
• Clinical Trial to Evaluate the Efficacy and Safety in Concomitant Administration of Macitentan and Dapagliflozin in Patients With Heart Failure With Mildly Reduced and Preserved Ejection Fraction (HFmrEF and HFpEF) and Combined Pre- and Post-capillary Pulmonary Hypertension (CpcPH)
  Recruiting · Phase 4 · Interventional · 64 enrolled · Gachon University Gil Medical Center
  NCT07147114updated 2026-04-03
• A Study to Assess Whether Macitentan Delays Disease Progression in Children With Pulmonary Arterial Hypertension (PAH)
  Completed · Phase 3 · Interventional · 165 enrolled · Actelion
  NCT02932410updated 2026-03-13
• Efficacy and Mechanisms of Macitentan for Non-Coronary Obstructive Angina
  Recruiting · Early phase 1 · Interventional · 40 enrolled · China-Japan Friendship Hospital
  NCT07392281updated 2026-02-06
• Clinical Study to Compare the Efficacy and Safety of Macitentan and Tadalafil Monotherapies With the Corresponding Fixed-dose Combination Therapy in Subjects With Pulmonary Arterial Hypertension (PAH)
  Completed · Phase 3 · Interventional · 187 enrolled · Actelion
  NCT03904693updated 2025-12-19
• Effects of Combination Medical Therapy Followed by BPA on Right Ventricular-PA Coupling and Hemodynamics in CTEPH
  Recruiting · Phase 3 · Interventional · 15 enrolled · Dr Sudarshan Rajagopal
  NCT05140525updated 2025-10-21
• COMPERA / COMPERA-KIDS
  Recruiting · Observational · 14,000 enrolled · Technische Universität Dresden
  NCT01347216updated 2025-08-24
• Data Analysis for Drug Repurposing for Effective Alzheimer's Medicines (DREAM) - PDE5
  Completed · Observational · 13,021 enrolled · Brigham and Women's Hospital
  NCT05039086updated 2025-08-06

Frequently asked questions

How does Macitentan work?

Endothelin (ET)-1 and its receptors (ET A and ET B ) mediate a variety of deleterious effects, such as vasoconstriction, fibrosis, proliferation, hypertrophy, and inflammation. In disease conditions such as PAH, the local ET system is upregulated and is involved in vascular hypertrophy and in organ damage.

What is Macitentan used for?

According to FDA labeling, Macitentan carries indications including: OPSUMIT is an endothelin receptor antagonist (ERA) indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) in adults to reduce the risks of disease progression and hospitalization for PAH ( 1.1 ). 1.1 Pulmonary Arterial Hypertension OPSUMIT is an endothelin receptor antagonist (ERA) indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) in adults to reduce the risks of disease progression and hospitalization for PAH.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Macitentan?

Macitentan is classified as Antihypertensives for pulmonary arterial hypertension, Endothelin Receptor Antagonist, Endothelin Receptor Antagonists, Decreased Blood Pressure, Pulmonary Arterial Vasodilation.

What are the brand names for Macitentan?

Macitentan is marketed under brand names including Opsumit, Opsynvi.

What are the contraindications for Macitentan?

Macitentan labeling lists contraindications including: Pregnancy ( 4.1 ) Hypersensitivity ( 4.2 ) 4.1 Pregnancy OPSUMIT may cause fetal harm when administered to a pregnant woman. OPSUMIT is contraindicated in females who are pregnant.. Always consult the full prescribing information and a clinician.